Role of endothelin-1 in a syndrome of myelofibrosis and osteosclerosis

Abstract

Context: Primary myelofibrosis is one of the chronic myeloproliferative disorders characterized by bone marrow fibrosis associated with extramedullary hematopoiesis and osteosclerosis. Endothelin-1 (ET1) is a potent vasoconstrictor that is also a key mediator of osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation. Case Description:Wereport laboratory, radiographic,bonedensitometry,andbonehistology data of a patient presenting with newly diagnosed, biopsy-proven myelofibrosis and osteosclerosis.We were able to demonstrate abundant ET1 signaling in the bones of our patient. Conclusions: We believe that ET1 is responsible for the osteosclerosis that develops with advanced myelofibrosis and suggest that ET1 signaling may play a role in other osteosclerotic settings as well.